This invention relates to pharmaceutical compositions in the form of a substantially amorphous composition of matter comprising a tetrahydrofuran azole antifungal (as well as esters and ethers thereof) and a polymer used as a polymer matrix.
WO 95/17407, published Jun. 29, 1995, discloses tetrahyrofuran antifungal compounds of Formula (I): ##STR3## wherein: X is independently both F or both Cl, or one X is independently F and the other is independently Cl; and R.sub.1 is a straight or branched chain (C.sub.3 to C.sub.8) alkyl group substituted by one or two hydroxy moieties; and ethers or esters thereof.
WO 95/17407 discloses that examples of suitable compositions of these compounds include solid compositions such as tablets and capsules. WO 95/17407 discloses that a solid carrier can be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders or tablet disintegrating agents; it can also be an encapsulating material. WO 95/17407 discloses that in a tablet, the active compound is mixed with a carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.
The oral bioavailability of active compounds can vary with the dosage form of the active compound. For example, it is known that solution dosages and suspensions generally give rise to higher bioavailability than capsules or tablets (see Pharmacokinetics Process and Mathematics, ACS Monograph 185, Chapter 5, page 57 (1986), and J.G. Nairn, Remington's Pharmaceutical Sciences, 18th edition (1990)). However, tablets and capsules are more convenient dosage forms, and it would be preferable to have a tablet or capsule dosage form of an active compound that has good bioavailability.
A pharmaceutical composition of the above described antifungal compounds that provides enhanced bioavailability of the antifungal compounds would be a contribution to the art. A pharmaceutical composition of the above antifungal compounds that can be manufactured in a tablet or capsule form that has greater bioavailability than a suspension would also be a contribution to the art. This invention provides these contributions to the art. Thus, this invention overcomes the problem of making active compounds such as a tetrahydrofuran azole antifungal that have a very low aqueous solubility more bioavailable.